Hello and welcome to week three of the Industrial Biotechnology MOOC, Biochemical and Bioprocess Engineering. This week, we're going to cover a general introduction to the background of bioprocessing, biochemical engineering, microbial fermentation and bioreactor design, biocatalysis and enzymatic processes, recovery of both large and small molecules, and finally process economics and scale up. So what is biochemical engineering? Biochemical engineering is about taking biological molecular transformations such as the transformation of glucose to ethanol by yeast. And it's about taking that transformation and designing a process around it at scale. So by that, I mean rather than making test tube amounts of our product of interest, ethanol in this case. We can make tonne amounts of our product of interest. And in order to design a successful biological process and scale it up, we need to understand something about constraint management as biochemical engineers. So this means understanding the physical phenomena, the standards in codes, the regulations that exist, in order to adhere to them. It also involves understanding process design, process conditions, and technology in order to design a plausible process. One that's going to make us our product of interest, the right amount, at the right quality, and at the right price. If we take this on now and start thinking about processes and systems, we can define what we mean by a process. So process a is a collection of one or more steps that's arranged in a sequence to carry out the desired molecular transformation of our raw materials into our products. So, for instance, it's about the processing steps required to transform glucose into ethanol, using yeast as a biocatalyst. Sometimes as chemical or biochemical engineers, we refer to these various stages as unit operations. So a unit operation is a part of a process that carries out a specific task or has a specific function. A system is a representation of a part or whole process which is chosen sensibly in order for us to evaluate what we call material balances. So material balances are the way we work out the material requirements of a process. As in how much ethanol do we produce for a given amount of glucose? Or put another way, if I know my product market, for ethanol in this case, is a certain number of tonnes per year. How much glucose do I need in order to make that amount of ethanol? Quite often, we define our system and call it a black box. Because we're not always, in the first instance, concerned with the detailed functioning of what happens in the system. We're just interested in what goes in and what comes out. The next level of detailed design is very much concerned with what happens within the system as well. So once we've calculated the material requirements of our bioreactor, the next step is actually to do the detailed design of that reactor itself. So how do we document and communicate process information? As biochemical engineers, we do this using a process flow diagram, PFD, or a flowsheet. So, how to interpret a PFD, and what do they look like? And how do we concisely present the relevant data, such as stream flow rates, compositions, temperatures and pressures? This is all vital information for us as biochemical engineers to understand a process design. And so what we do is we take the information and we put it on a flowsheet. So here there's an example of a generic, simplified process flow diagram for a batch fermentation process. And if you take a moment to look at this, we can see that there's a flow. So material moves from the sterilizer to the fermenter through the centrifuge to a separation column, where we recover our products and our byproducts. Now, if we take a moment to define some systems here, and look at the different stages of the process. First of all we see that there's some pre-treatment, or proprietary stages, where we have growth medium. That gets fed through a sterilizer and charged into our fermenter or bioreactor. We also have our inoculum, so it's the cells, in our example that we've been using here, it would be the yeast cells, that we're going to put into the fermenter in order to transform the glucose in the growth medium into ethanol, which is our product of interest. That material gets charged, or loaded, into the fermenter and that's where we carry out our biological transformation. So the design of that fermenter is such that it enables the desired molecular transformation to be carried out, i.e., it maximizes our yield of ethanol. After the production stage, we move on to the final stage of this simple process, which is what we call downstream separation. So here, we're separating, or recovering, the ethanol, which is our product (the thing we want to sell) from the byproducts that we've produced during the process. So as we move through the flowsheet we can see we have a strategy to transform glucose, our raw material, into our ethanol, our product. And we've got various unit operations in here, such as the bioreactor, or the product separation column. And we've got various systems that we can define as well. So now I'd like to introduce you and talk more about this concept of material balance. And to understand this we're going to take something that we already know how to do intuitively. And give us a framework to actually do this material balance, calculate the material requirements of a process in a much more rigorous way. So the question is, how do you keep track of the number of people on a bus? So if I'm Manchester City Council, we're interested in bus usage statistics then I'm going to put you on the bus to Stockport. And at the end of the day I want the statistics, so I want to know how many people are on the bus after every stop. There's a couple different strategies you could adopt here, and one would be after every stop, to run around the bus and do a head count. A more sensible strategy might be to sit at the front of the bus, count the number of people that get on the bus at every stop. So say five people get on the bus, and at the same stop count the number of people that get off the bus. So say three people get off the bus at this given stop. From the difference between those two numbers, so five people on and three people off, we know that there's two extra people on the bus. What we're actually doing here, is we're doing a material balance on people. So here our conserved quantity is people and our system is the bus. So we're going to take this concept on now. And you might realize that this is the same sort of concept that we apply when we keep track of the amount of money we might have in a bank account. The difference between our incomings and our outgoings gives us the amount of money that's in that account. So if we take this concept forward now and define properly what a material balance is. So we're saying a material balance is a balance of the conserved quantity for a system. So, the system is the entity over which we construct our balance, so it was the bus in this case. What do you mean by a conserved quantity? So it's something that is unchanged by the system, and it's neither created nor destroyed. So when we talk about material balances, the quantity we're really thinking about is mass. And what do we mean by balance? Well, balance is a mechanism through which we equate this conserved quantity. So in the bus example, the bus was our system, our conserves quantity was people. And we balance the number of people getting on with the number of people getting off the bus. So if we think about how we might formalize that intuitive concept a little bit. We can form something called the general material balance equation. Which shows the difference between what enters the system through the system boundaries, leaves the system through the system boundaries is generated within the system, or consumed within the system, is equal to the accumulation or the buildup within the system. So in our bus example, input minus output equalled accumulation. Five people got on the bus, three people got off, so our accumulation, or the actual number of people on the bus, was two. The generation and consumption terms come in when we have biological reaction. So if we're trying to do a glucose balance on our bioreactor, then we'd have a consumption term. And if we were doing an ethanol balance, then we'd have a generation term, because our product is generated, or made within the fermenter. This is really a key learning point here, because to actually solve material balance problems, this is the only equation that you need. And quite often, as we saw with the example with the bus, some of the terms can be eliminated. So we can simplify this. But this is always our starting point. So, if we think a little bit now about types of processes. This will allow us to actually think about how we might be able to simplify that general material balance equation. So we can say a process is at steady state, if all process variables are constant with respect to time. So, for example, that might mean things like mass flow rates, pressure, composition. So for every stream in a process, all these things are constant with respect to time. On the other hand, we also have transient processes which cover anything else. So this is a process that's not at steady state. Where process variables are not constant with respect to time. And it's important not to confuse steady state with equilibrium. So to finish off, I'd like to give another example of a material balance to enable you to see how we apply this general material balance equation. So in this example, we're going to consider the population of Greater Manchester. And we're going to say that every year 50,000 people move into Greater Manchester, 70,000 people move out, 22,000 people are born, and 23,000 people die. So the questions are: What is the system? What is the conserved quantity? And what is the balance over a year? So we know that our system is the boundary of Greater Manchester. Could get a map and look that up. And our conserve quantity is people. And again we have our general material balance equation. In minus out plus generation minus consumption equals accumulation. And here we can see that 50,000 people move into Manchester every year, so that's the input into our system. 70,000 people move out of Greater Manchester every year, so that's our output term. There's 22,000 births, our generation term, so generated inside our system boundary. 23,000 people die, that gives us a consumption term. And that is equal to the accumulation. And in this case you'll see that when we sum those numbers together, we find that 21,000 people a year leave Greater Manchester. So that's the significance there of the minus sign, because we've defined things going into our system across the system boundary as positive. So we can see that the population of greater Manchester is decreasing by 21,000 people per year. A little question to leave you with, which is, can we draw other balances on this system? So that's the end of this introductory unit. The thing to realize here is that we've introduced flowsheets, the concept of molecular transformation and constraint management, in order to design a process. And I've really introduced you to the general concepts of material balances. The next step is really to think about how we can apply these material balances to describe processes and work out the material requirements of processes.